After a few years of flawless operation, one day our 2009 27" iMac suddenly refused to boot. I determined that the hard drive, a Seagate model that was the subject of a recall, had started to fail. I bought a new drive to replace it and pulled up the iFixIt guide for that model.
I proceeded very slowly and deliberately with this repair, partially due to the incompatibility of my thick fingers with the tiny ribbon cables and connectors that must be removed during the disassembly. I had previously done similar drive replacements on G5 iMacs, but the Intel iMacs are a much different beast.
The repair took a couple of hours, but each step proceeded smoothly due to the excellent guide. My only regret is not owning a clean room - it was impossible to get the screen 100% lint-free before slapping it back into place, but at least no cat hair was trapped inside (a miracle in our house). I updated the guide with a few helpful hints learned during my experience.
Before ordering a replacement drive, I had read that the drive must be from the same manufacturer as the one being replaced, otherwise the fan control might not work. While software workarounds were mentioned, I decided to play it safe and bought another Seagate, even though I was wary of them from the original drive failure and a similar Seagate failure on a MacBook.
To help ease my concerns, I finally got my backup house in order. I already had online backups through CrashPlan, so I wasn't in danger of losing data from the failed drive, but I was not up to date on local bootable backups and had never set up Time Machine. This significantly delayed my recovery from the failure, so after the repair I immediately rectified that situation with external drives dedicated to those backups. If you aren't already good with multiple backups on-site, off-site, and online, take care of that now.